title: ATG7 deficiency promote apoptotic death induced by Cisplatin in human esophageal squamous cell carcinoma cells.
abstract: Cisplatin-(DDP)-based adjuvant chemotherapy is widely used for the treatment of esophageal cancer. However, DDP-based combinatorial treatments can eventually result in tumor resistance response. Therefore, new therapeutic strategies and/or new adjuvant drugs still need to be explored. In this study, we aimed to understand the role of autophagy in ESCC cells resistance to Cisplatin and discuss its potential therapeutic implication. We found that exposure to Cisplatin induced a significant increase in LC3 formation. While the proliferation of ESCC cells was inhibited upon Cisplatin exposure, inhibition of autophagy by ATG7 interference further increased the sensitivity to chemotherapy. Meanwhile, the Cisplatin-induced apoptotic cell death was significantly enhanced. These results suggest that autophagy may function importantly in ESCC cells resistance to Cisplatin. Intriguingly, the resistance could be recovered by autophagy inhibition. This also points to potential therapy for ESCC by perturbing autophagy.
authors.affiliation: Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, 200025 Shanghai, China. drczy1952@hotmail.com
authors.forename: Lianggang
authors.initials: L
authors.lastname: Zhu
authors.forename: Hailei
authors.initials: H
authors.lastname: Du
authors.forename: Minmin
authors.initials: M
authors.lastname: Shi
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Chen
authors.forename: Junbiao
authors.initials: J
authors.lastname: Hang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D000071193:Autophagy-Related Protein 7; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D017024:Chemotherapy, Adjuvant / Q000379:methods; D002945:Cisplatin / Q000627:therapeutic use*; D022162:Cytoplasmic Vesicles; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000502:physiology; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D055785:Gene Knockdown Techniques; D006801:Humans; D034622:RNA Interference; D044764:Ubiquitin-Activating Enzymes / Q000172:deficiency* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes; D002945:Cisplatin
keywords: ATG7; Cisplatin; apoptosis; autophagy; esophageal squamous cell carcinoma